A New Treatment For Alzheimer’s Improves How Drugs Reach The Brain

Forbes Innovation Science A New Treatment For Alzheimer’s Improves How Drugs Reach The Brain Gabriel A. Silva Contributor Opinions expressed by Forbes Contributors are their own. I write about neuroscience and its intersection with technology. Following Click to save this article. You'll be asked to sign into your Forbes account.

Got it Jan 14, 2024, 01:07pm EST Share to Facebook Share to Twitter Share to Linkedin Memory loss in Alzheimer's Disease. getty Alzheimer's Disease is a neurodegenerative disorder that, in advanced stages, devastates memory and cognitive functions. Despite much research over many decades, it remains clinically challenging to manage, with different treatment strategies showing mixed and limited results.

Alzheimer's Disease is characterized by the accumulation of amyloid beta plaques and neurofibrillary tangles — which consist of abnormally elevated levels of a protein called tau — in the brain. Alzheimer's affects millions worldwide, with numbers expected to continue rising as populations age.

According to the Center for Disease Control and Prevention , there were an estimated 6.7 million Americans aged 65 years or older who had Alzheimer’s Disease in 2023. They project this number to triple to about 14 million people by 2060. A significant challenge in treating Alzheimer's is the blood brain barrier , a protective boundary formed by the blood vessels that feed the brain and spinal cord, that hinders the delivery of potentially therapeutic drugs.

This is not a unique challenge for Alzheimer's. The systemic delivery of drugs and medicines, such as those taken orally or by other routes that deliver them into the bloodstream, that need to reach the brain and spinal cord will be met by the blood brain barrier. However, in a recent paper published in The New England Journal of Medicine , Ali R.

Rezai and colleagues present encouraging results showing that ultrasound can temporarily disrupt the blood brain barrier. Doing so long enough allowed them to deliver a key Alzheimer's drug called aducanumab, an anti amyloid antibody, to reach the brain. The combined approach resulted in decreased amyloid beta plaques in treated regions.

The Blood Brain Barrier — A Crucial Brain Protector that Sometimes Gets in the Way The blood brain barrier's serves to protect the brain and spinal cord, which together make up the central nervous system, from things like pathogens and toxins. Unfortunately, the barrier also prevents most drugs from reaching the brain, making it a significant challenge to treat many neurological disorders, including Alzheimer's.

The authors of this work temporarily opened the blood brain barrier by using low intensity focused ultrasound, guided by magnetic resonance imaging, or MRI, to facilitate the delivery of aducanumab to targeted brain regions. The study only tested a very small number of patients diagnosed with mild Alzheimer's, three to be exact, over six months.

So, it was a proof of concept trial rather than a large clinical study. Given the number of patients involved, no population statistics or generalizations can be drawn from their results. However, given the positive clinical responses of the three patients who underwent the treatments and how carefully the study was planned and conducted, it certainly offers encouragement and warrants a larger follow up study with more patients.

MORE FOR YOU New Samsung Leak Justifies Brave Galaxy S24 Ultra Downgrade Today’s NYT ‘Connections’ Hints And Answers (Sunday, January 14) The Best Mattresses Of 2024 Tested By Our Sleep Experts The blood brain barrier is a physical and functional barrier formed by the endothelial cells that line the capillaries in the brain and spinal cord.

Connections tightly join these cells together, which are actually called tight junctions. Tight junctions give endothelial cells control over what crosses from the blood into the cerebrospinal fluid the brain and spinal cord are floating in, selectively regulating substances that can cross while blocking others.

However, in the context of Alzheimer's and other central nervous system diseases, this barrier also restricts therapeutic agents' access, presenting a significant challenge for drug delivery. At the same time, dysregulation and disruption of the barrier are associated with the pathophysiology of Alzheimer's and other neurodegenerative disorders.

Focused Ultrasound for Drug Therapy in the Brain Focused ultrasound is a non invasive method that temporarily disrupts the blood brain barrier. In the current study, the authors used MRI guided focused ultrasound. This approach allows for precise targeting of the ultrasound waves to specific brain regions.

This precision is vital because indiscriminate opening of the barrier could lead to unpredictable and adverse side effects. The ability to open the blood brain barrier in a controlled way represents a significant advancement in neuropharmacology. It allows drugs to be directly delivered to affected brain regions in a highly targeted way.

Aducanumab, the drug used in this research, is an FDA approved drug for the treatment of Alzheimer's Disease. Aducanumab targets and reduces amyloid beta plaques in the brain if it can cross the blood brain barrier and reach it. The researchers wanted to test if they could improve the therapeutic effect of aducanumab by taking advantage of focused ultrasound to improve its delivery.

While limited to the three patients, the study's results were promising. Using positron emission tomography — PET — brain imaging to measure the levels of amyloid beta plaques, the researchers showed a decrease in amyloid in regions treated with focused ultrasound compared to regions that did not receive ultrasound treatment.

Cognitive testing following treatments was more inconclusive. Two patients showed no changes, while the third patient showed some cognitive decline throughout the study. This is not necessarilky surprising or alarming, since the intent of the study was to measure levels of amyloid beta plaques in treated versus none treated areas of the brain.

In effect, the study was not designed to give the patients a full brain treatment. In addition, the researchers wanted to see if the combined ultrasound aducanumab protocol was safe with no unforseen side effects. They showed that overall it was neurologically safe in the participating patients. The potential impact of this work goes well beyond its immediate results.

Combining focused ultrasound with drug therapy could offer a significant new approach to the treatment of central nervous system neurological disorders where the blood brain barrier poses a considerable obstacle. This would open up new avenues for exploring other drugs that were previously ineffective due to their inability to cross the barrier.

Over the years, there has been much work aimed at transiently disrupting the blood brain barrier or molecularly 'tricking' it to get drugs across. This research includes the development of various nanotechnology methods . However, for the most part, this work has had limited clinical success, partly due to safety considerations about the technologies being used.

Ultrasound, in particular low energy focused ultrasound, offers significant safety advantages over other methods in this regard. From Lab to Clinic: The Challenges and Road Ahead However, it is important to recognize that, while certainly encouraging and exciting, this was a preliminary proof of concept study with a very limited cohort of patients.

Considerable additional work and research needs to be done before this approach will lead to practical clinical adoption. For example, one of the key concerns is the long term safety of repeatedly opening the blood brain barrier by any method. This may be necesary, however, in the case of a drug that needs to be administered on a regular basis.

The integrity of the blood brain barrier is crucial for brain health. Additionally, while this study showed a reduction in amyloid beta plaque levels, the correlation between amyloid reduction and improvement in the cognitive symptoms of Alzheimer's is still an area of active research. In other words, decreasing the levels of amyloid by itself may not be sufficient to slow down or reverse cognitive decline because there may be other molecules involved in the pathology.

This, in turn, may necessitate delivering other drugs or even completely other therapeutic approaches. Nonetheless, this approach is a promising line of research that warrants serious consideration. It may one day offer patients and their families clinical choices that are impossible today. Follow me on LinkedIn .

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